title: Sources of thrombomodulin in pre-eclampsia: renal dysfunction or endothelial damage?
abstract: A plethora of evidence exists to show that endothelial perturbations underlie many of the clinical features of pre-eclampsia (P-EC), and consequently the markers signifying endothelial disturbance exhibit a rise in plasma. Among others, plasma thrombomodulin (TM) level rises significantly. TM is a transmembrane glycoprotein expressed abundantly on the endothelium of the microvasculature. It neutralizes the thrombotic potential of thrombin, mediating this anticoagulant effect through activation of protein C. Endothelial injury results in a localized loss of TM with a focal impairment of protein C activation and resultant thrombotic tendency. Mainly expressed on the endothelial cells, a small amount of TM is found in plasma with levels rising in certain pathological conditions. Although elevation in levels of TM can be due to endothelial TM proteolysis secondary to endothelial insult, ineffective clearance may account for this in renal and hepatic dysfunction. In P-EC not only is there ongoing endothelial injury, but renal function is also affected. To establish the cause of elevated TM level in P-EC, three groups of pregnant women were investigated. It appears that the elevation in plasma TM is not related to renal or hepatic dysfunction in P-EC. It is more likely that plasma TM is derived from placental or vascular endothelial cells subsequent to activation or damage, confirming the hypothesis that damage to vascular endothelial cells is the primary underlying cause of P-EC.
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Brazil. lucim@farmacia.ufmg.br
authors.forename: Luci
authors.initials: L
authors.lastname: Dusse
authors.forename: Lara
authors.initials: L
authors.lastname: Godoi
authors.forename: Rashid S
authors.initials: RS
authors.lastname: Kazmi
authors.forename: Patrícia
authors.initials: P
authors.lastname: Alpoim
authors.forename: Juliane
authors.initials: J
authors.lastname: Petterson
authors.forename: Bashir A
authors.initials: BA
authors.lastname: Lwaleed
authors.forename: Maria
authors.initials: M
authors.lastname: Carvalho
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011486:Protein C / Q000378:metabolism; D018180:Thrombomodulin / Q000097:blood*; D014508:Urea / Q000097:blood
chemical_list: D011486:Protein C; D018180:Thrombomodulin; D014508:Urea; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase